Articular cartilage is a type of hyaline cartilage that lines the surfaces of the opposing bones in a diarthrodial joint (e.g. knee, hip, shoulder, etc.). Articular cartilage provides a near-frictionless articulation between the bones, while also functioning to absorb and transmit the compressive and shear forces encountered in the joint. Further, since the tissue associated with articular cartilage is aneural, these load absorbing and transmitting functions occur in a painless fashion in a healthy joint.
However, when articular cartilage tissue is no longer healthy it can cause debilitating pain in the joint. Cartilage health can be affected by disease, aging, or trauma, all of which primarily involve a breakdown of the matrix consisting of a dense network of proteoglycan aggregates, collagen type 11 fibers, and other smaller matrix proteins. Cartilage cells, called chondrocytes, are unable to induce an adequate healing response because they are unable to migrate, being enclosed in lacunae surrounded by a dense matrix. Further, since the tissue is avascular, initiation of healing by circulating cells is not possible.
Several cartilage repair strategies have been attempted in the past. These include surgical techniques such as microfracturing or performing an abrasion arthroplasty on the bone bed to gain vascular access, and hence, stimulate extrinsic repair in the defective region.
Another surgical technique is mosaicplasty or osteochondral autograft transfer system (OATS). In this case, cylindrical plugs of healthy cartilage from a low-load bearing region of the knee are taken and transplanted into the defective region.
The only FDA-approved cartilage treatment in the market involves autologous chondrocyte implantation (CartiCel™). Autologous chondrocyte implantation involves performing an initial biopsy of healthy cartilage from the patient, isolating the cells from the tissue, expanding the cells in vitro by passaging them in culture, and then reintroducing them into the defective area. The cells are retained within the defect by applying a periosteal tissue patch over the defect, suturing the edges of the patch to the host tissue, and then sealing with fibrin glue. The healing observed is similar to that observed with microfracture or abrasion of the bone bed, indicating that it is the preparation of the bone bed and not the introduction of the cells that facilitates the healing process.
Tissue engineering strategies for healing cartilage are being investigated by several academic and commercial teams and show some promise. The approach primarily involves using a carrier or a scaffold to deliver cells or stimulants to the defect site. The scaffold material can be a purified biologic polymer in the form of a porous scaffold or a gel (purified collagens, glycoproteins, proteoglycans, polysaccharides, or the like in various combinations) or porous scaffolds of synthetic biodegradable polymers (PLA, PGA, PDS, PCL, or the like in various combinations). Several challenges remain with this approach, however. Some of these challenges include retention of the active stimulant at the defect site, inability to control the rate of release of the stimulant (resulting in tissue necrosis due to overdose), cytotoxicity of the cells due to the degradation by-products of the synthetic polymers.
As alluded to above, it is known to use various collagen scaffolds to provide a scaffold for repair and regeneration of damaged tissue. U.S. Pat. No. 6,042,610 to ReGen Biologics, hereby incorporated by reference, discloses the use of a device comprising a bioabsorbable material made at least in part from purified natural fibers. The purified natural fibers are crosslinked to form the device. The device can be used to provide augmentation for a damaged meniscus. Related patents U.S. Pat. Nos. 5,735,903, 5,479,033, 5,306,311, 5,007,934, and 4,880,429 also disclose a meniscal augmentation device for establishing a scaffold adapted for ingrowth of meniscal fibrochondrocyts.
It is also known to seed collagenous scaffolds with cells. See, e.g., U.S. Pat. Nos. 6,379,367 and 6,283,980, the disclosure of each of which is hereby incorporated by reference.
It is also known to use naturally occurring extracelluar matrices (ECMs) to provide a scaffold for tissue repair and regeneration. One such ECM is small intestine submucosa (SIS). SIS has been used to repair, support, and stabilize a wide variety of anatomical defects and traumatic injuries. Commercially available SIS material is derived from porcine small intestinal submucosa that remodels to the qualities of its host when implanted in human soft tissues. Further, it is taught that the SIS material provides a natural scaffold-like matrix with a three-dimensional microstructure and biochemical composition that facilitates host cell proliferation and supports tissue remodeling. Indeed, SIS has been shown to contain biological molecules, such as growth factors and glycosaminoglycans, that aid in the repair of soft tissue in the human body. SIS products, such as OASIS and SURGISIS, are commercially available from Cook Biotech Inc., Bloomington, Ind.
Another SIS product, RESTORE® Orthobiologic Implant, is available from DePuy Orthopaedics, Inc. in Warsaw, Ind. The DePuy product is described for use during rotator cuff surgery, and is provided as a resorbable framework that allows the rotator cuff tendon to regenerate. The RESTORE Implant is derived from porcine small intestine submucosa, a naturally occurring ECM (composed of mostly collagen type I (about 90% of dry weight), glycosaminoglycans and other biological molecues) that has been cleaned, disinfected, and sterilized. During seven years of preclinical testing in animals, there were no incidences of infection transmission from the implant to the host, and the SIS material has not adversely affected the systemic activity of the immune system.
While small intestine submucosa is readily available, other sources of ECM are known to be effective for tissue remodeling. These sources include, but are not limited to, stomach, bladder, alimentary, respiratory, and genital submucosa, or liver basement membrane. See, e.g., U.S. Pat. Nos. 6,379,710, 6,171,344, 6,099,567, and 5,554,389, each of which hereby incorporated by reference.
For the purposes of this disclosure, it is within the definition of a naturally occurring ECM to clean and/or comminute the ECM, or to cross-link the collagen within the ECM. However, it is not within the definition of a naturally occurring ECM to separate and purify the natural fibers and reform a matrix material from purified natural fibers. Also, while reference is made to SIS, it is understood that other naturally occurring ECMs, such as stomach, bladder, alimentary, respiratory, or genital submucosa, or liver basement membrane, for example, whatever the source (e.g. bovine, porcine, ovine, etc.) are within the scope of this disclosure. Thus, as used herein, the terms “naturally occurring extracellular matrix” or “naturally occurring ECM” are intended to refer to extracellular matrix material that has been cleaned, disinfected, sterilized, and optionally cross-linked. The terms “naturally occurring extracellular matrix” and “naturally occurring ECM” are also intended to include ECM foam material prepared as described in copending U.S. patent application Ser. No. 10/195,354 entitled “Porous Extracellular Matrix Scaffold and Method”, filed concurrently herewith.
The following patents, hereby incorporated by reference, disclose the use of ECMs for the regeneration and repair of various tissues: U.S. Pat. Nos. 6,379,710; 6,187,039; 6,176,880; 6,126,686; 6,099,567; 6,096,347; 5,997,575; 5,993,844; 5,968,096; 5,955,110; 5,922,028; 5,885,619; 5,788,625; 5,733,337; 5,762,966; 5,755,791; 5,753,267; 5,711,969; 5,645,860; 5,641,518; 5,554,389; 5,516,533; 5,460,962; 5,445,833; 5,372,821; 5,352,463; 5,281,422; and 5,275,826.
It is known to use such materials as catgut and SIS to make appliances. See the Bolesky published application WO 95/06439. The Bolesky application discloses devices that are semi-rigid and are formed into desired shapes, but Bolesky does not disclose a process for fabricating naturally occurring extracellular matrix parts so that they are rigid and hardened.